IC50: 15nM: inhibits phosphoinositide 3-kinase α (PI3Kα) in vitro.
INK1117 is a novel, potent and selective inhibitor of PI3Kα with potential antineoplastic activity, which may induce tumor cell apoptosis and growth inhibition in PI3Kα-expressing tumor cells. INK1117 dampens signaling to Akt and suppresses the growth of cancer cells harboring wild-type or mutated p110α. PI3Ks, a family of eight lipid kinase enzymes, produce 3-phosphorylated phosphoinositides in cellular membranes and are promising targets for therapeutic development in cancer.
In vitro: INK1117 blocked class I PI3K enzymes (p110α, p110β, p110γ or p110δ) in the low to mid-nanomolar range in human natural killer (NK) cell lines. INK1117 selectively inhibited PI3K signaling in cellular assays when used at 0.1-1 μM. INK1117 selectively dampened p110 α when used at 1 μM. INK1117 did not inhibit production of IFN-γ protein in cells with anti-NKG2D, indicating that INK1117 did not decrease IFN-γ mRNA [1].
In vivo: Female C57BL/6 mice were orally given INK1117 at a dose of 60 mg/kg using a sterile disposable 20G-1.5” feeding needle. After 8 days, INK1117 had negligible effects on NK cell maturation or survival. However, INK1117 did not show significantly decrease in the percentage of B cells and did not alter the percentages of T cells or the fractions of CD4 and CD8 T cells, the percentages of NK cells in bone marrow and spleen [1].
Reference:
[1]. Yea, S., So, L., Mallya, S., Lee, J., Rajasekaran, K., Malarkannan, S., & Fruman, D. Effects of Novel Isoform-Selective Phosphoinositide 3-Kinase Inhibitors on Natural Killer Cell Function. Plos ONE. 2014; 9(6): e99486.